I. Information Relating to Previous Patents and Applications
Several aminosterol compositions have been isolated from the liver and stomach of the dogfish shark, Squalus acanthias. One important aminosterol, squalamine, is the subject of U.S. Pat. No. 5,192,756 to Zasloff, et al., which patent is entirely incorporated herein by reference. That patent describes the antibiotic properties of squalamine. Since the discovery of squalamine, several interesting properties of this compound have been discovered. For example, as described in U.S. Pat. Nos. 5,733,899 and 5,721,226, squalamine may function as an antiangiogenic agent. These patents are entirely incorporated herein by reference. Additional uses of squalamine (e.g., as an NHE3 inhibiting agent and as an agent for inhibiting the growth of endothelial cells) are disclosed in U.S. Pat. No. 5,792,635 and U.S. patent application Ser. No. 08/840,706 (filed Apr. 25, 1998, entitled “Treatment of Carcinomas Using Squalamine in Combination with Other Anti-cancer Agents,” in the names of Michael Zasloff and Jon Williams) and continuation of this application Ser. No. 09/150,724 filed Sep. 10, 1998 and PCT Application US99/20645. These applications also are entirely incorporated herein by reference.
Methods for synthesizing squalamine have been devised, such as the methods described in WO 98/24800 (published Jun. 10, 1998) and in U.S. Patent Appl. No. 60/032,378. This PCT publication and the U.S. patent application are entirely incorporated herein by reference. The PCT application relates to U.S. patent application Ser. No. 08/985,876, which application also is entirely incorporated herein by reference. Additionally, U.S. Pat. No. 5,792,635 also discloses squalamine isolation and synthesis techniques.
Stemming from the discovery of squalamine, other aminosterols have been discovered in the dogfish shark liver and stomach and have been investigated. One important aminosterol that has been isolated and identified has the structure shown in FIG. 1. In this application, the compound having the structure shown in FIG. 1 will be referred to as “compound 1436” or simply “1436.” This compound has the general molecular formula C37H72N4O5S and a calculated molecular weight of 684.53017.
Compound 1436 previously has been described in U.S. Pat. Nos. 5,795,885, 5,763,430, and 5,847,172. Each of these U.S. patents is entirely incorporated herein by reference. These U.S. patents describe the structure of compound 1436 and other aminosterols, as well as processes for synthesizing and isolating compound 1436 and related aminosterols. For example, compound 1436 may be prepared from squalamine as starting material. Additional methods for synthesizing compound 1436 (as well as squalamine) are described in U.S. Provisional Patent Appl. No. 60/032,378, filed Dec. 6, 1996, which application is entirely incorporated herein by reference.
As further described in these patents and patent applications, compound 1436 has a variety of interesting properties. For example, compound 1436 has been found to be capable of inhibiting mitogen-induced mouse, dog or human T-lymphocyte proliferation, as well as being capable of inhibiting the proliferation of a variety of other cells and tissues.
II. Information Relating to this Application
Compound 1436 and other aminosterol compounds isolated from the dogfish shark liver and stomach have been found to possess interesting antibiotic and anti-proliferative properties with respect to a variety of cells and tissues. These interesting properties of compound 1436 have prompted applicants to conduct further investigation into the uses and properties of this compound.
In addition to treating various ailments and diseases, such as viral based ailments and diseases, cancers, and arthritis, compound 1436 has been found to have other favorable properties and effects. As one specific example, applicants have found that compound 1436 may be used to reduce weight gain in mammals and in a mouse model of type II diabetes to prevent weight gain and to maintain blood glucose at normal levels. The weight gain of the animals in these studies was controlled due to reduction of net food consumption and they were apparently healthy, viable animals.